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The extraordinary and unique properties of persistent luminescent (PerLum) nanostructures like storage of charge carriers, extended afterglow, and some other fascinating characteristics like no need for in-situ excitation, and rechargeable luminescence make such materials a primary candidate in the fields of bio-imaging and therapeutics. Apart from this, due to their extraordinary properties they have also found their place in the fields of anti-counterfeiting, latent fingerprinting (LPF), luminescent markings, photocatalysis, solid-state lighting devices, glow-in-dark toys, etc. Over the past few years, persistent luminescent nanoparticles (PLNPs) have been extensively used for targeted drug delivery, bio-imaging guided photodynamic and photo-thermal therapy, biosensing for cancer detection and subsequent treatment, latent fingerprinting, and anti-counterfeiting owing to their enhanced charge storage ability, in-vitro excitation, increased duration of time between excitation and emission, low tissue absorption, high signal-to-noise ratio, etc. In this review, we have focused on most of the key aspects related to PLNPs, including the different mechanisms leading to such phenomena, key fabrication techniques, properties of hosts and different activators, emission, and excitation characteristics, and important properties of trap states. This review article focuses on recent advances in cancer theranostics with the help of PLNPs. Recent advances in using PLNPs for anti-counterfeiting and latent fingerprinting are also discussed in this review.